Dopaminergic neurons in the nigrostriatal system show a pronounced age- related degeneration. Oxidative stress is theorized to precipitate or escalate this neuronal loss. Experiments to test this hypothesis directly by characterizing oxidative damage to proteins and lipids in regions containing these neurons, the putamen and substantia nigra, in postmortem human brain are proposed. In addition, an innovative strategy will be used to compare oxidative stress in dopaminergic and non-dopaminergic neurons in the putamen by measuring damage to proteins and lipids in synaptic vesicles derived from these neurons. Oxidative damage will be measured by biochemical assays for protein carbonyl content, protease sensitivity, and lipid peroxidation products. To assess the function of synaptic vesicles during aging, proton pumping and dopamine storage in the vesicles will be assessed by methods in routine use in this laboratory.